P1279: OUTCOMES OF AUTOLOGOUS STEM CELL TRANSPLANT IN PATIENTS WITH MULTIPLE MYELOMA WITH TWO OR MORE HIGH-RISK CYTOGENETIC ABNORMALITIES
Authors: Oren Pasvolsky, Sassine Ghanem, Denái R. Milton, Adeel Masood, Mark R. Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Jeremy L. Ramdial, Yago Nieto, Hans C. Lee, Krina K. Patel, Partow Kebriaei, Sheeba K. Thomas, Donna M. Weber, Robert Z. Orlowski, Elizabeth J. Shpall, Richard E. Champlin, Muzaffar H. Qazilbash
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Patients with multiple myeloma (MM) and high-risk (HR) cytogenetic abnormalities have inferior outcomes, and are under-represented in clinical trials. There is paucity of data regarding outcomes of MM patients with multiple HR abnormalities undergoing autologous stem cell transplant (autoSCT). Aims: To evaluate outcomes of autoSCT in patients with newly diagnosed MM and two or more HR abnormalities. Methods: We conducted a retrospective, single-center analysis of adult HRMM patients that received autoSCT between 2008-2018. HR cytogenetics were defined as del17p, t(4;14), t(14;16), 1q21 gain or amplification (1q+) by fluorescence in situ hybridization. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Associations between OS and PFS and measures of interest were determined using Cox proportional hazards regression models. Measures that occur after autoSCT were included in the regression models as time-dependent covariates. Results: Seventy-nine patients with HRMM were included in our analysis, with a median age of 61 (range 33.5-76.5) years and 57% were female. Sixty-seven patients had two HR cytogenetic abnormalities, while 12 had three abnormalities. The most common combinations of HR abnormalities were [1q+, t(4:14)] (n=25, 32%) and [1q+, del 17p] (n=21, 27%). The most common induction regimens used were VRD (48%) and KRD (16%). Prior to autoSCT, 52 patients (66%) achieved ≥VGPR, while 23 patients (29%) achieved MRD negative ≥VGPR pre-transplant. Fifty-six (71%) patients received post-transplant maintenance therapy (Table 1). At day 100 post autoSCT and at best post-transplant responses, 36 patients (46%) and 40 patients (51%) achieved MRD negative ≥VGPR, respectively. With a median follow-up in surviving patients of 38.3 (range: 11.9 to 104.8) months, the median PFS and OS in the entire cohort were 22.9 and 71.5 months, respectively (Figure 1). For the subset of patients with three HR abnormalities, the median PFS was 15.6 months and median OS was 28.0 months. Achieving MRD negative ≥VGPR either prior to autoSCT (hazard ratio 0.35; p=0.007) or at best response after autoSCT (HR 0.50; p=0.037), were associated with improved PFS in univariate analysis (UVA), but not in multivariable analysis (MVA). In UVA for OS, male gender (HR 0.37; p=0.025), younger age (HR 0.48, p: 0.012), presence of 1q+ (HR 0.43; p=0.045) and achieving MRD negative ≥VGPR post autoSCT (HR 0.30; p=0.010) were associated with significantly better OS. On MVA, only male gender (HR 0.31; p=0.030) and achieving MRD negative ≥VGPR post autoSCT (HR 0.30; p=0.034) remained significant. Summary/Conclusion: MM patients with ≥ 2 HR abnormalities have a median PFS of <24 months with the current standard of care, and may require novel treatment modalities, including CAR-T and bispecific antibodies, earlier in their disease course.Keywords: Cytogenetic abnormalities, High risk, Multiple myeloma, Autologous hematopoietic stem cell transplantation